In order to fully appreciate events that occur during Alzheimer's disease (AD) pathogenesis it is critical to understand the relationships between the various cell types and molecules involved and the pathological hallmarks of the disease. One way to better understand these complex relationships is to visualize them in vivo, in real time, while blocking or augmenting the function of particular molecules that are potentially involved in these relationships. To this end, we propose to use in vivo multiphoton imaging of a murine brain containing AD- like pathology to visualize interactions between microglia, neurons, and neuronal processes in real time. This will enable us to determine how specific molecules present within the milieu of the AD brain affect the structure and function of these cell types. We hypothesize that the interaction between apoE and aggregated beta-amyloid is dynamic and regulates microglial motility and cytokine release that results in ongoing injury to neuronal processes. Elucidation of how microglial cell morphology and motility as well as neuronal injury are affected by aggregated beta-amyloid, apoE and specific cytokines produced by microglia will be explored in vivo. [unreadable] [unreadable] [unreadable]